There are two specific aims of this research project. The first is to evaluate the effects of coronary vasodilators (nitroglycerin, nifedipine and verapamil) on cerebral blood flow and auto-regulation, intracranial pressure and cerebral arterial diameter, under normal conditions and in conditions of experimental cerebral ischemia and experimental cerebral vasospasm. This experimental work is necessary because of the increasing use of these drugs in patients with ischemic coronary disease despite an inadequate knowledge of their effects on the above parameters of the cerebral circulation. In addition, the clinical success of these drugs in patients with ischemic coronary disease suggests that they may be useful in clinical states of cerebral ischemia and vasospasm. The experimental methods to be used include the hydrogen clearance method for measuring cerebral blood flow in normal and acutely ischemic states in the dog and monkey and an angiographic model for studying normal cerebral vessels in the monkey and chronic experimental vasospasm in the dog. These models have been developed in our laboratory and are currently in use. The second specific aim of this project is to study the effectiveness of nitroglycerin in the prevention of symptomatic cerebral vasospasm following subarachnoid hemorrhage in humans. To date, there is no effective curative or preventive therapy of this serious complication. We feel we have developed a reliable CT scan method of telling which patient will develop severe vasospasm following subarachnoid hemorrhage. Because our preliminary data suggests that nitroglycerin effectively relieves experimental cerebral vasospasm in the dog, we are now in a position to conduct a randomized clinical trial using this drug to try to prevent cerebral vasospasm in the high risk patients. Should this drug prove to be effective as a preventative agent, its potential benefit will be enormous.